The DOI matches its Crossref record, with a small difference in title or year; 24 of the 25 references it cites were found in a registry or an index.
Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.
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“No difference in the primary outcome of mean SOFA score change at 72 h post enrolment was observed.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [525]
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“A patient-level analysis of two of the randomized PEEP trials (440, 441) suggested that patients with ARDS who respond to increased PEEP with improved oxygenation have a lower risk of death; this association was stronger in patients with more severe ARDS (PaO 2 /FiO 2 < 150 mm Hg) compared with patients with less severe ARDS (444).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [440]
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“At 30 days, 34.7% (35/101) of patients randomised to combination therapy had died vs. 29.3% (29/99) randomised to placebo (HR, 1.3; 95% CI 0.8–2.2; p = 0.26).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [525]
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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
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Metadata
- Authors
- Moskowitz, A., Huang, D. T., Hou, P. C., Gong, J., Doshi, P. B., Grossestreuer, A. V., Andersen, L. W., Ngo, L., Sherwin, R. L., Berg, K. M., Chase, M., Cocchi, M. N., McCannon, J. B., Hershey, M., Hilewitz, A., Korotun, M., Becker, L. B., Otero, R. M., Uduman, J., Sen, A., Donnino, M. W., & for the ACTS Clinical Trial Investigators
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Pittsburgh (US)
- Brigham and Women's Hospital (US)
- Hofstra University (US)
- The University of Texas Health Science Center at Houston (US)
- Wayne State University (US)
- Mount Auburn Hospital (US)
- South Shore Hospital (US)
- Oakland University (US)
- Henry Ford Health (US)
- Mayo Clinic (US)
- Corresponding author
- Donnino, Michael W.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-08-18
- Volume
- 324
- Issue
- 7
- Pages
- 642
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7435341
- OpenAlex
- W3069087306
- Semantic Scholar
- a9205794d79affdd861a6a28192f566070b621c8
- Cited by
- 253
- References
- 25
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 25 · 2023: 37 · 2022: 57 · 2021: 75 · 2020: 11
- FWCI
- 32.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- University of Pittsburgh
- Open Philanthropy Project
- National Institutes of Health
- National Institute of General Medical Sciences (K23GM128005)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- septic shock, vitamin C, cortisol, thiamine, organ failure, SOFA score, renal failure, 30-day mortality, combination therapy, sepsis
- MeSH terms
- Adrenal Cortex Hormones, Adult, Aged, Ascorbic Acid, Cross Infection, Drug Therapy, Combination, Female, Humans, Hyperglycemia, Hypernatremia, Male, Middle Aged, Multiple Organ Failure, Shock, Septic, Thiamine, Proportional Hazards Models, Treatment Failure, Organ Dysfunction Scores
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